The development of new drugs to treat disease relies on the discovery of new targets indicative of a disease condition or process. Identifying valid disease targets is difficult as the genetic and biochemical changes that cause disease are often quite subtle, perhaps involving many minor modifications in several genes. Current technologies are not sensitive to small changes in the genome. We will create large libraries of genes derived from cDNA and display the expressed polypeptides on the surface of a filamentous bacteriophage. The genes of interest will be discriminated from undesired genes by using a large library of cognate binding proteins displayed on complementary phage. Using this simultaneous cloning system we will be able to dynamically survey, in a single test tube, trillions of interactions between potential targets and cognate binding receptors. Only pairs of positively interacting components are reproduced. After several rounds of selection we will narrow the number of potential targets and individual clones will be analyzed in detail to derive potential disease markers or drug discovery leads. In Phase I studies we will test the feasibility of the concept using a series of tumor cell lines which differ in their ability to metastasize.
We will develop a new method to clone genes relevant to disease processes. This method may lead to the discovery of the root causes of many diseases which have a genetic component including cancer and heart disease.
